Granted Patent B2

US 7,482,353 · App. 11/452,443 · Granted Jan 27, 2009

Abstract

Claims (67)

1. A method comprising:

a) alkylating a substituted or unsubstituted 3-aminopyrazole-4-carbonitrile compound with a halo acetate compound of the formula:

wherein,

W is hydrogen;

R 1 is an alkyl group, an alkenyl group, an alkynyl group, a heteroalkyl group, a heteroalkenyl group, a heteroalkynyl group, an aryl group, a heteroaryl group, an arylalkyl group or a heteroarylalkyl group;

Hal is Cl, Br or I; and

each X 1 is O.

2. The method of claim 1 , wherein R 1 is methyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, allyl, trimethylsilyl, tert-butyldimethylsilyl or phenyl.

3. The method of claim 1 , wherein one of the products of the reaction is a substituted or unsubstituted heterocyclic compound of the formula:

wherein,

W is hydrogen;

R 1 is hydrogen or an alkyl group, an alkenyl group, an alkynyl group, a heteroalkyl group, a heteroalkenyl group, a heteroalkynyl group, an aryl group, a heteroaryl group, an arylalkyl group or a heteroarylalkyl group; and

X 1 is O.

4. A method comprising:

a) reacting a substituted or unsubstituted heterocyclic compound of the formula:

with a substituted or unsubstituted compound of the formula:

or a substituted or unsubstituted compound of the formula:

wherein the reaction produces a substituted or unsubstituted heterocyclic compound of the formula:

wherein,

W is hydrogen;

W′ is hydrogen or —NH 2 ;

R 1 is an alkyl group, an alkenyl group, an alkynyl group, a heteroalkyl group, a heteroalkenyl group, a heteroalkynyl group, an aryl group, a heteroaryl group, an arylalkyl group or a heteroarylalkyl group;

H—Ac is an acidic group capable of protonating the diamine; and

X 1 is O.

5. The method of claim 4 , wherein the solvent for the reaction is compound IVb, methanol, ethanol, n-propanol, isopropanol or t-butanol, N,N-dimethylformamide (DMF) or dimethylsulphoxide (DMSO).

6. The method of claim 4 , wherein the reaction is allowed to reflux.

7. The method of claim 4 , further comprising:

b) protecting the exocyclic amine of the substituted or unsubstituted heterocyclic compound V with a amine protecting group to thereby produce a compound of the formula:

wherein,

W is hydrogen;

Pg 1 is an amine protecting group;

R 1 is an alkyl group, an alkenyl group, an alkynyl group, a heteroalkyl group, a heteroalkenyl group, a heteroalkynyl group, an aryl group, a heteroaryl group, an arylalkyl group or a heteroarylalkyl group; and

X 1 is O.

8. The method of claim 7 , wherein the amine protecting group is Fmoc, Bhoc, Z, t-boc or Cyoc.

9. The method of claim 4 , further comprising:

b) converting the ester group of compound V to a carboxylic acid group to thereby produce a substituted or unsubstituted heterocyclic compound of the formula:

wherein,

W is hydrogen; and

X 1 is O.

10. The method of claim 7 , further comprising:

c) converting the ester group of compound VI to a carboxylic acid group to thereby produce a substituted or unsubstituted heterocyclic compound of the formula:

wherein,

W is hydrogen;

Pg 1 is an amine protecting group; and

X 1 is O.

11. The method of claim 10 , wherein Pg 1 is Fmoc, Bhoc, Z, t-boc or Cyoc.

12. A method comprising:

a) reacting the carbonyl carbon of the activated carboxylic acid group or active ester group of a substituted or unsubstituted heterocyclic compound of the formula:

with the secondary nitrogen of a substituted or unsubstituted N-(2-aminoethyl)glycine moiety,

wherein,

W is hydrogen;

Pg 1 is an amine protecting group;

R 2 is —SH, —OH or an active ester leaving group; and

X 1 is O.

13. The method of claim 12 , wherein the substituted or unsubstituted N-(2-aminoethyl)glycine moiety has the formula:

wherein,

Pg 2 is an amine protecting group;

each Y 1 is independently hydrogen, an alkyl group, an alkenyl group, an alkynyl group, a heteroalkyl group, a heteroalkenyl group, a heteroalkynyl group, an aryl group, a heteroaryl group, an arylalkyl group or a heteroarylalkyl group;

Y 2 is hydrogen or a protected or unprotected amino acid side chain;

R 3 is —OH, —SH, —SR 1 or —OR 1 , wherein R 1 is an alkyl group, an alkenyl group, an alkynyl group, a heteroalkyl group, a heteroalkenyl group, a heteroalkynyl group, an aryl group, a heteroaryl group, an arylalkyl group or a heteroarylalkyl group; and

X 1 is O.

14. The method of claim 13 , wherein R 1 is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, sec-butyl, allyl, trimethylsilyl, tert-butyldimethylsilyl or phenyl.

15. The method of claim 12 , wherein the substituted or unsubstituted N-(2-aminoethyl)glycine moiety is a PNA subunit of a PNA oligomer.

16. The method of claim 12 , wherein, Pg 1 is Fmoc, Bhoc, Z, t-boc or Cyoc.

17. The method of claim 13 , wherein Pg 1 is Fmoc, Bhoc, Z, t-boc or Cyoc and wherein Pg 2 is different from Pg 1 and Pg 2 is independently Fmoc, Bhoc, Z, t-boc, Cyoc or trityl.

18. The method of claim 12 , wherein the active ester leaving group is a group of the formula:

wherein X 1 is O.

Assignments (9)